How to diagnose peripheral neuropathy?

From the Guidelines

To rule out neuropathy, a comprehensive evaluation is necessary, including a detailed medical history, physical examination, and specific diagnostic tests, as recommended by the most recent guidelines 1.

Key Components of Evaluation

The evaluation should start with a consultation with a healthcare provider to assess symptoms such as numbness, tingling, burning sensations, or weakness in extremities.

• The physical examination typically includes testing reflexes, muscle strength, sensitivity to touch, vibration, and temperature.
• Diagnostic tests may include nerve conduction studies (NCS) and electromyography (EMG), which measure how well electrical impulses travel through nerves and muscles.
• Blood tests are often ordered to check for conditions that can cause neuropathy, such as diabetes (hemoglobin A1C), vitamin deficiencies (B12, folate), thyroid dysfunction, and autoimmune disorders.

Specific Recommendations

According to the latest standards of care in diabetes-2023 1, all people with diabetes should be assessed for diabetic peripheral neuropathy starting at diagnosis of type 2 diabetes and 5 years after the diagnosis of type 1 diabetes, and at least annually thereafter.

• Assessment for distal symmetric polyneuropathy should include a careful history and assessment of either temperature or pinprick sensation (small-fiber function) and vibration sensation using a 128-Hz tuning fork (for large-fiber function).
• Annual 10-g monofilament testing should be performed to identify feet at risk for ulceration and amputation.

Importance of Early Diagnosis

Early diagnosis is crucial because treating the underlying cause can prevent further nerve damage, as emphasized in the standards of medical care in diabetes-2020 1 and reinforced by the 2023 guidelines 1.

• Some neuropathies are reversible if the underlying condition is addressed promptly, while others may require symptomatic management with medications like gabapentin, pregabalin, or duloxetine to control pain and discomfort.
• It is also important to consider causes of neuropathy other than diabetes, as outlined in the 2018 standards of medical care in diabetes 1, to provide comprehensive care.

From the Research

Ruling Out Neuropathy

To rule out neuropathy, a comprehensive approach is necessary, involving a detailed history of symptoms, family and occupational history, and a neurological as well as general physical exam 2. The following steps can be taken:

• Pattern recognition of various neuropathies can help to build a differential diagnosis based on the presentation, including acute versus chronic, primary demyelinating versus axonal, hereditary versus acquired, asymmetric versus symmetric, presence of facial palsies, sensory or motor predominant, and presence of prominent autonomic symptoms 2.
• Nerve conduction studies and electromyography (NCS/EMG) is the primary diagnostic tool in the evaluation of patients with large-fiber polyneuropathy 2.
• Laboratory workup includes serum studies and potentially cerebrospinal fluid, genetic studies, immunological markers, and fat pad biopsy for select patients 2.
• Skin biopsy may be used to assess intraepidermal nerve fiber density if small-fiber neuropathy is suspected, and nerve biopsy may be useful in select cases 2.
• Magnetic resonance imaging and neuromuscular ultrasound have also shown promise in the evaluation of peripheral neuropathy 2.

Clinical Evaluation

Clinical evaluation is one of the best available tools for assessment and diagnosis of neuropathic pain 3. This includes:

• A thorough history that includes medical, functional, and psychosocial evaluations 3.
• Physical and neurologic examination, including an assessment of spontaneous pain, pain evoked by daily activities, and other abnormal sensations 3.
• Sensitivity to pinprick, touch, pressure, cold, heat, and vibration are measured, often confirming the suspected diagnosis 3.

Diagnostic Approach

A stepwise approach to the evaluation and workup of peripheral neuropathy is recommended 4. This includes:

• A comprehensive history, physical examination, and judicious laboratory testing 4.
• Early peripheral neuropathy may present as sensory alterations that are often progressive, including sensory loss, numbness, pain, or burning sensations in a "stocking and glove" distribution of the extremities 4.
• Initial laboratory evaluation includes a complete blood count, comprehensive metabolic profile, fasting blood glucose, vitamin B12, and thyroid-stimulating hormone levels, and serum protein electrophoresis with immunofixation 4.
• Referral to a neurologist for additional testing, such as electrodiagnostic studies, specific antibody assays, or nerve biopsy, may be necessary if the initial evaluation is inconclusive 4.

Treatment and Management

Treatment of peripheral neuropathy focuses on managing the underlying etiology 4. This may include:

• Medications, such as gabapentinoids and antidepressants, to alleviate neuropathic pain 4, 5.
• Gabapentin at doses of 1800 mg to 3600 mg daily can provide good levels of pain relief to some people with postherpetic neuralgia and peripheral diabetic neuropathy 5.
• Individual adverse events, such as dizziness, somnolence, peripheral oedema, and gait disturbance, may occur with gabapentin 5.

Examination and Clinical Care

Examination of a patient with peripheral neuropathy starts with careful questioning of the patient about the history of symptoms and signs and of a possible familial disorder 6. This includes:

• Determining the pattern of neuropathy and site of lesions, including roots, nerve trunks, focal, multifocal, length-dependent generalized polyneuropathy 6.
• Identifying the type of nerve fibers predominantly affected, the association with trophic changes and autonomic dysfunction, and the course of the disease 6.
• Deciding which investigations seem necessary and their timing, including electrophysiological tests, imaging, CSF examination, blood tests, nerve and muscle biopsy, DNA testing, etc. 6.